The invention relates to a microfabricated device for use in measuring the physical properties of compound samples, where the properties measured using such devices are those which involve partitioning of the compound between two phases, measuring partition coefficients, distribution coefficients, acid-base dissociation constants, solubility and vapour pressure.
The biologically active compound, for example a pharmaceutical or agrochemical compound, depends on a range of physicochemical and biopharinaceutical attributes of that compound which governs the bioavailability of the compound in the target and non-target species or tissue or organism or at a target or non-target enzyme or molecule. In order to accelerate the rate of discovery of such molecules, there is currently considerable interest in the measurement of such properties for large numbers of compounds very early in the discovery process so that these factors may be used to influence future decisions on which molecules to synthesis as potential candidates for drug or agrochemical research programs.
Synthetic techniques such as multiple parallel synthesis (MPS) and combinatorial chemistry provide relatively small sample sizes, for example in the microgram range. The limited sample sizes currently produced are not large enough to supply more than a few tests within the drug discovery process before the supply is exhausted. Therefore, resynthesis may be required in order to restock the chemical library.
Candidate compounds of potential interest may therefore only be available in relatively small amounts i.e.  less than 1 mg. There is therefore a strong need for methods that can be applied to large numbers of compounds without requiring proportionately more resources and which are capable of dealing with small sample weights. Conventional methods often employ complex separation steps which are time-consuming. Although these can be automated, the serial nature of the analysis i.e. one sample at a time, still effectively limits the throughput.
Microfabrication techniques are generally known in the art using tools developed by the semiconductor industry to miniaturise electronics, it is possible to fabricate intricate fluid systems with channel sizes as small as a micron. These devices can be mass-produced inexpensively and are expected to soon be in widespread use for certain simple analytical tests. See, e.g., Ramsey, J. M. et al. (1995), xe2x80x9cMicrofabricated chemical measurement Systems,xe2x80x9d Nature Medicine 1:1093-1096; and Harrison, D. J. et al (1993), xe2x80x9cMicromachining a miniaturized capillary electrophoresis-based chemical analysis system on a chip,xe2x80x9d Science 261:895-897. In addition devices have been proposed for preparative, analytical and diagnostic methods which bring two streams of fluid in laminar flow together which allows molecules to diffuse from one stream to the next, examples are proposed in W09612541, WO9700442 and U.S. Pat. No. 5716852.
Miniaturisation of laboratory techniques is not a simple matter of reducing their size. At small scales different effects become important, rendering some processes inefficient and others useless. It is difficult to replicate smaller versions of some devices because of material or process limitations. For these reasons it is necessary to develop new methods for performing common laboratory task on the microscale.